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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Metabolism in Rats of 3-Phenoxybenzyl Alcohol and 3-Phenoxybenzoic Acid Glucoside Conjugates Formed in Plants
Author:
Nobuyoshi Mikami, Jun Yoshimura, Hideo Kaneko, Hirohiko Yamada and Junshi Miyamoto
Year:
1985
Bibliographic source:
Pestic. Sci. 1985, 16, 33-45

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
The objective of the experiment was to study the metabolism in Rats of 3-Phenoxybenzyl Alcohol
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
[14C]3-Phenoxybenzyl alcohol
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: 10% Tween 80 (1 ml)
Details on exposure:
The specific-pathogen free (SPF) and germ-free rats were each given a single oral dose of the 14C-preparations of 3-Phenoxybenzyl alcohol in 10% Tween 80 (1 ml) at a rate of 9 µmol kg-1. The SPF rats were individually housed in all-glass metabolism cages. The urine and faeces were collected separately for 1 day (germ-free rats), and for up to 7 days (SPF rats). At least four SPF and two germ-free rats were sacrificed at specified intervals for determination of 14C excretion and tissue residues, or for characterisation of the I4C metabolites.
Duration and frequency of treatment / exposure:
7 days
Doses / concentrations
Remarks:
Doses / Concentrations:
9 µmol kg-1
No. of animals per sex per dose:
No data
Control animals:
not specified

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
3-phenoxybenzyl alcohol was absorbed from the gastrointestinal tracts of the SPF rats.
Type:
distribution
Results:
Metabolites formed were distributed in the urine, bile and faeces.
Type:
metabolism
Results:
Following absorption, 3-phenoxybenzyl alcohol was rapidly oxidised to 3-phenoxybenzoic acid.
Type:
excretion
Results:
99.4 (+ 0.6) of the administered radioactivity was excreted after 7 days of administration

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
 3-phenoxybenzoic acid and
 3-(4-sulphonyloxyphenoxy)benzoic acid

Any other information on results incl. tables

Further details on metabolism

Following absorption, 3-phenoxybenzyl alcohol was rapidly oxidised to3-phenoxybenzoic acid. The acid was further metabolised by direct conjugation with glucuronide, and by hydroxylation primarily at the 4-position of the phenoxy ring, and subsequent conjugation with glucuronide and sulphate. The sulphate ester

3-(4-sulphonyloxyphenoxy)benzoic acid was rapidly eliminated in the urine, while the glucuronides were excreted in the bile and then cleaved in the gastrointestinal tract to afford 3-(4-hydroxyphenoxy)benzoic acid, which was reabsorbed and excreted in the urine as 3-(4-sulphonyloxyphenoxy)benzoic acid. These results were in good accord with those of the previous report. The sulphate conjugate 3-(4-sulphonyloxyphenoxy)benzoic acid was also excreted in the bile but to a lesser extent.However, it was fairly resistant to hydrolysis by the gut microflora, as compared with the glucose and glucuronide conjugates, and consequently corstituted a main metabolite of the intestinal contents and faeces

of the SPF rats. The sulphate codjugate 3-(4-sulphonyloxyphenoxy)benzoic acid was also a main faecal metabolite of the germ-free rats.

Meanwhile, the major metabolites were3-phenoxybenzoic acidand 3-(4-sulphonyloxyphenoxy)benzoic acid in the liver, and3-phenoxybenzoic acidin the blood.

3-Phenoxybenzyl alcohol (I) rapidly declined to the non-detectable level because of its rapid conversion to3-phenoxybenzoic acid.

Further details on excretion

The radioactivity excreted in the urine and faeces of SPF intact rats as % of the dose administered, following single oral administration of14C-3-phenoxybenzy1 alcohol is presented below:

0-1  day

In urine: 85.9 (+3.3)

In Feaces: 10.1(+3.3)

Total: 95.9 (+0.1)

0-7 days

Total: 99.4(+0.6)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
In an experiment to study the metabolism in Rats of 3-Phenoxybenzyl Alcohol, male SD rats were given a single oral dose of the 14C-preparations of 3-Phenoxybenzyl Alcohol in 10% Tween 80 (1 ml) at a rate of 9 µmol kg-1. The administered 3-Phenoxybenzyl Alcohol was absorbed in the GI tract and metabolized to 3-phenoxybenzoic acid and 3-(4-sulphonyloxyphenoxy) benzoic acid. At the end of 7 days, a total of 99.4 (+ 0.6) of the % of the dose administered was excreted out of the body of rats in urine and feaces.
Thus, it is concluded that the bioaccumulation potential of the chemical 3-Phenoxybenzyl Alcohol is expected to be low.
Executive summary:

In an experiment to study the metabolism in Rats of 3-Phenoxybenzyl Alcohol, male SD rats weregiven a single oral dose of the14C-preparationsof 3-Phenoxybenzyl Alcoholin 10% Tween 80 (1 ml) at a rate of 9 µmol kg-1. The administered3-Phenoxybenzyl Alcohol was absorbed in the GI tract and metabolized to3-phenoxybenzoic acidand 3-(4-sulphonyloxyphenoxy)benzoic acid. At the end of 7 days, a total of 99.4(+0.6)of the % of the dose administered was excreted out of the body of rats in urine and feaces.

Thus, it is concluded that the bioaccumulation potential of the chemical3-Phenoxybenzyl Alcoholis expected to be low.